Several methods have been developed for introducing exogenous DNA molecules into eukaryotic cells in order to take advantage of the widespread benefits arising from the application of recombinant DNA technology to the production of transgenic organisms. These methods include physical, non-biological systems such as electroporation, microinjection, calcium phosphate or polyethylene glycol (PEG) mediated DNA uptake or cell fusion, and microprojectile bombardment (aka "biolistics") and modified biological systems such as Agrobacterium-mediated T-DNA transfer to plant cells (for a general and somewhat dated overview, see chapters 2 and 3 of "Plant Genetic Transformation and Gene Expression, A Laboratory Manual", ed. by Draper, J. et al., pub. by Blackwell Scientific Publications (1988); see also Potrykus, et al., "Direct Gene Transfer: State of the Art and Future Potential", Plant Mol. Biol. Rep. 3: 117-128 (1985)).
The methods which have been developed have allowed the stable transformation of a wide variety of organisms with exogenous DNA. In particular, the development of physical techniques such as microprojectile bombardment has overcome apparent host-range limitations imposed by biological systems. However, a common deficiency of these physical methods is that they do not provide any means for ordered integration of the delivered DNA into the cell genome. Consequently these methods must depend upon uncontrolled integration of the delivered DNA by poorly understood mechanisms, causing exogenous DNA to be integrated as multiple copies of random fragments usually at a single site in the cell genome.
Improving the predictability of stable transformation events arising from the physical introduction of exogenous DNA into the cell would significantly improve the utility and overall efficiency of these processes for producing genetically stable transformed organisms exhibiting stable expression of transgenes. One approach which has been taken to accomplish this goal has been to combine proteins which promote transformation and/or integration in biological systems with non-biological delivery techniques. In order to achieve the desired effect, it has been considered necessary to associate the proteins themselves with the exogenous DNA molecules in advance of delivery to the transformation target cell, thus mimicking as closely as possible the biological system from which the proteins are derived (see, e.g. international application no. PCT/EP94/02566 to Hohn et al. published Feb. 23, 1995 as WO 95/05471; international application no. PCT/US95/07543 to Conary, J. et al. published Dec. 21, 1995 as WO 95/34647).